title: Endogenous insulin-like growth factor-I is obligatory for stimulation of rat inhibin alpha-subunit expression by follicle-stimulating hormone.
abstract: Insulin-like growth factor-I (IGF-I) is essential for FSH-dependent steroidogenesis by rat granulosa cells (GC), but whether IGF-I is required for other FSH-dependent functions is unknown. To investigate the role of IGF-I in the mechanisms of FSH-stimulated inhibin alpha-subunit (Inh-alpha) production, rat GC were cultured with FSH, IGF-I, insulin-like growth factor-binding protein (IGFBP)-4, IGFBP-5, and/or anti-IGF-I antibody. Inh-alpha protein and mRNA levels were measured in conditioned medium and cells by Western immunoblotting and Northern analysis, respectively. Inh-alpha expression was increased by FSH (3.5-fold) and IGF-I (2.5-fold), and the effects were dose and time dependent. FSH stimulation of Inh-alpha was attenuated by IGFBP-4 or -5 in a dose-dependent fashion, and the effects were reversed by IGF-I. Anti-IGF-I antibody mimicked the inhibitory effects of IGFBP-4 and -5. Forskolin, cholera toxin, and 8-bromo-cAMP increased Inh-alpha production approximately 3.5-fold, and the effects were blocked by IGFBP-4 or -5. Increases in Inh-alpha by FSH, IGF-I, forskolin, cholera toxin, and 8-bromo-cAMP were totally blocked by the protein tyrosine kinase inhibitor, tyrphostin A23. In summary, these results suggest that the stimulation of Inh-alpha expression by FSH requires activation of protein tyrosine kinases by endogenously produced IGF-I. We propose that the IGF-I signaling is obligatory for FSH stimulation of Inh-alpha expression in rat GC.
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, La Jolla 92093-0674, USA.
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.forename: T
authors.initials: T
authors.lastname: Kubo
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Shimasaki
authors.forename: G F
authors.initials: GF
authors.lastname: Erickson
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002396:Catechols / Q000494:pharmacology; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D015870:Gene Expression; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D007265:Inhibins / Q000235:genetics* / Q000378:metabolism; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000494:pharmacology; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020032:Tyrphostins
chemical_list: D002396:Catechols; D004791:Enzyme Inhibitors; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D009570:Nitriles; D012333:RNA, Messenger; D020032:Tyrphostins; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D007265:Inhibins; D007334:Insulin-Like Growth Factor I; D005640:Follicle Stimulating Hormone; D002772:Cholera Toxin; D011505:Protein-Tyrosine Kinases; C060641:tyrphostin A23